Developmental functions of rapgef1b in neural crest specification and presomitic mesoderm patterning

Rapgef1, a cell fate determinant and effector of multiple signaling events is essential for mammalian embryonic development. Here, we investigated the developmental role of rapgef1 using zebrafish as a model. We show that rapgef1 is maternally expressed and alternately spliced isoforms of its two paralogs, rapgef1a and rapgef1b show development and tissue-specific expression. CRISPR-Cas9 and morpholino-based targeting of rapgef1b resulted in developmental defects in the embryonic brain and somites. The rapgef1b morphants showed altered expression of lineage determinants of the cranial neural crest. Comparative transcriptome and altered expression analysis of morphants revealed fresh insights into the developmental functions of rapgef1b in presomitic mesoderm, and somitogenesis. During early embryonic mitoses, the morphants showed mitotic defects such as diffused spindle poles and chromosome mis-congression. Our results demonstrate that rapgef1b is required for normal embryonic mitoses, cranial neural crest specification, somitogenesis, and myogenesis during embryonic development. SignificanceRAPGEF1 is an important signaling factor, essential for cytoskeletal remodeling, signaling, and cell adhesion in cultured mammalian cells. The Rapgef1 knockout mice embryos fail to survive beyond implantation, strongly suggesting its essential role in embryonic development. Further, mutations in RAPGEF1 are associated with many neurological disorders like schizophrenia and intellectual disability with behavioral defects. However, the role of rapgef1 in regulating embryonic events is poorly understood. This study highlights the developmental functions of rapgef1 in lineage determination during embryonic development. We show that rapgef1b acts as an activator of canonical Wnt signaling and is essential for early neurodevelopment and somite formation. Further, rapgef1b is also required to maintain mitotic fidelity, spindle pole integrity, and chromosome congression during embryonic mitoses.